1. Field of the Invention
The present invention relates to a method for using Product R as hereinafter defined to treat patients having rheumatoid arthritis.
2. Description of the Related Art
Autoimmune diseases in mammals can generally be classified in one of two different categories: cell-mediated disease (i.e. T-cell) or antibody-mediated disorders. Non-limiting examples of cell-mediated autoimmune diseases include multiple sclerosis, rheumatoid arthritis, autoimmune tyroiditis, diabetes mellitus (Juvenile onset diabetes) and autoimmune uveoretinitis. Antibody-mediated autoimmune disorders include myasthenia gravis and systemic lupus erythematosus (or SLE).
Diseases with autoimmune features affect well over 5 percent of individuals at some time in their life. A large group of disparate autoimmune diseases are characterized by an often intense, sustained and injurious immune response apparently directed to a self-antigen. Autoimmunity is not a generalized state, but rather each disease reflects a highly specific pattern of recognition of different self structures and likely reflects equally distinct immune recognition events. These disorders vary from relatively mild conditions to those that virulently attack critical cells and organs of the body.
Autoimmune diseases may be classified as organ specific or non-orgain specific depending on whether the response is primarily against either antigens localized to particular organs or widespread antigens. In organ specific diseases typified by Hashimoto's thyroiditis, lesions are restricted because the antigen in the organ acts a target for immunological attack. In non-organ specific disease typified by systemic lupus erythematosus (SLE), complexes formed with the antigens involved are deposited systemically, particularly in the kidney, joints and skin, so giving rise to the more diseminated features of the disease.
Systemic lupus erythematosus (SLE) is an inflammatory, multisystem disease characterized clinically as a relapsing disease of acute or insidious onset that may involve any organ in the body. Clinically, symptoms are due to disease affecting the skin, kidneys, serosal membranes, joints and heart. Anatomically, all sites have in common vascular lesions with fibrinoid deposits and immunologically, the disease involves antibodies of autoimmune origin, especially antinuclear antibodies (ANA). The ANA are directed against both DNA and RNA. Autoantibody development appears to be multifactorial in origin, involving genetic, hormonal, immunologic and environmental factors.
Rheumatoid arthritis is a systemic, chronic, inflammatory disease that affects principally the joints and sometimes many other organs and tissues throughout the body. The disease is characterized by a nonsuppurative proliferative synovitis, which in time leads to the destruction of articular cartilage and progressive disabling arthritis. The disease is caused by persistent and self-perpetuating inflammation resulting from immunologic processes taking place in the joints. As is the case with most autoimmune diseases the trigger that initiates the immune reaction remains unidentified. Both humoral and cell mediated immune responses are involved in the pathogenesis of rheumatoid arthritis. The majority of patients have elevated levels of serum immunoglobulins and essentially all patients have an antibody called rheumatoid factor (RF) directed against a component of another antibody class.
Multiple sclerosis is another disease that is thought to be caused by autoimmune mechanisms. The cause of multiple sclerosis is unknown but seems to be multifactorial. Susceptibility or resistance may be genetically determined; something in the environment interacts with the human host at the proper age to cause biochemical and structural lesions in the central nervous system. The systemic immune response and the response of the central nervous system become involved. Although the cause and pathogenesis of, multiple sclerosis are unknown, it is widely believed that immune abnormalities are somehow related to the disease. Three possible mechanisms have been postulated: infection, autoimmunity, and a combination of the two. Suppression or modulation of the immune responses may be the key.
Myasthenia gravis is an autoimmune disorder caused by antibodies directed against the acetylcholine receptor of skeletal muscle. Present information indicates at least three mechanisms whereby acetyicholine receptor antibody may interfere with neuromuscular transmission and thus induce myasthenia gravis. Acetylcholine receptor antibody pay interfere (directly or indirectly) with acetylcholine receptor function. In both experimental allergic myasthenia gravis and human myasthenia gravis, the extent of acetylcholine receptor loss parallels the clinical severity of the disease, suggesting that acetylcholine receptor antibody-induced acceleration of acetylcholine receptor degradation is important in the development of myasthenia gravis. Complement-mediated destruction of the postsynaptic region is the third possible cause. Other disorders, especially those presumed to be autoimmune in origin, can occur in association with myasthenia gravis. Thyroid disease, rheumatoid arthritis, systemic lupus erythematosus, and pernicious anemia all occur more commonly with myasthenia gravis than would be expected by chance.
Implication of viruses in auto immunity has been supported by findings that autoimmune responses are induced, accelerate or enhanced concomitant with infection by a wide variety of human DNA and RNA viruses. Using an investigative approach that focuses on one potential mechanism where microbes cause autoimmunity, or molecular mimicry, a number of etiologic agents have been identified as potential causes of autoimmune disease.
Certain viruses have a mitogenic effect on unique lymphocyte subsets and hence act as polyclonal activators. Viruses can also infect lymphocytes and macrophage and directly or through their proteins cause release of lymphokines and manikines. These molecules can modulate immune responses in a variety of ways, including as growth or differentiation factors or by regulating MHC class I and/or class II expression on cells. Finally, microbial agents share determinants with host self proteins. In this instance, an immune response mounted by the host against a specific determinant of the infecting agent may cross-react with the mimic (shared) host sequence, leading to autoimmunity and, in some cases, tissue injury and disease.
The current treatments for both categories of autoimmune diseases involve administration of drugs which non-specifically suppress the immune response. Examples of such drugs are methotrexate, cyclophosphamide, Imuran (azathioprine) and cyclosporin A., steroid compounds such as prednisone and methylprednisilone are also employed in many instances. These drugs have limited efficacy against both cell- and antibody-mediated autoimmune diseases. Use of such drugs is limited by virtue of their toxic side effects and also because they induce “global” immunosuppression in a patient receiving prolonged treatment with the drug, e.g. the normal protective immune response to pathogenic microorganisms is downregulated thereby increasing the risk of infections caused by these pathogens. A further drawback is that there is an increased risk that malignancies will develop in patients receiving prolonged global immunosuppression.
Reticulose® emerged as an antiviral product in the 1930's. While it was originally believed to be a product composed of peptone, peptides and nucleic acids, the precise composition remains unidentified. Nevertheless, Reticulose® has demonstrated an ability to inhibit rapidly the course of several viral diseases. It is nontoxic, miscible with tissue fluids and blood sera and free from anaphylactogenic properties. Product R is a refinement of Reticlose® prepared by an improved manufacturing process. It is a peptide nucleic acid preparation with defined composition.
Insofar as the applicant knows, Product R has never been used, nor suggested for treating autoimmune diseases.